Calcitonin (abbreviated as CT) is a peptide hormone which participates in metabolism of minerals such as calcium and phosphorus and which is found in the thyroid glands of mammals and the ultimobranchial glands of birds and cartilaginous fishes.
The structures of calcitonins mainly originating from the thyroid glands of mammals have been identified for swine (Potts et al, Pro. Natl. Acad. Sci. USA 59: 1321-1328, 1968), humans (Neher et al, Nature 220: 984-996, 1968), bovines (Brewer et al, Biochemistry 63: 940-947, 1969), sheep (Potts et al, Calcium, Parathyroid Hormone and the Calcitonin: 121-127, 1972), and rats (Raulais et al, Eur. J. Biochem. 64: 607-611, 1976).
The structures of calcitonins mainly originating from the ultimobranchial glands have been identified for salmon (Niall et al, Pro. Natl. Acad. Sci. USA 64: 771-778, 1969), eels (Kotani et al, J. Biochem. 79: 345-352, 1976), and fowl (Homma et al, J. Biochem. 100: 459-467, 1986).
As shown in FIG. 1, the calcitonins which have heretofore been identified can be classified into three lineages: a swine lineage including swine, bovines, and sheep, a human lineage including humans and rats, and a salmon lineage including salmon, eels, and fowl. Each of these calcitonins is a single-chain polypeptide consisting of 32 amino acids in which the first and seventh amino acids are linked through a disulfide bond (S--S bond) to form a seven-membered ring with prolineamide present at the carboxyl terminus.
The above-described calcitonins are known to participate in the metabolic regulation of blood serum calcium and the bone metabolism. It has recently been found that, in addition to these activities, calcitonins also have an analgesic activity as a neurotransmitter and an antiulcer activity through calcium metabolism. However, the activities of calcitonins have not been elucidated completely. It is also known that the intensities of physiological activities of calcitonins greatly differ among the above-described lineages, e.g., in such a manner that those calcitonins originating from the ultimobranchial glands are much more potent than those calcitonins originating from the thyroid grands. For example, salmon calcitonin has an activity for decreasing the blood calcium level in humans which is about 30 times as high as that of human calcitonin.
Some calcitonins such as salmon and eel calcitonins or their derivatives have been commercially produced by means of chemical synthesis or genetic engineering, and they are available and used for treatment of osteoporosis and similar diseases. However, it is expected that these prior-art calcitonins lose their activities due to an increase in antibody level caused by long-term administration thereof. Accordingly, for therapeutic use of calcitonins, it is desired to find a novel calcitonin which does not belong to any of the above-described lineages of calcitonins. Such a novel calcitonin will be helpful in investigations to elucidate the physiological activities of calcitonins.